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61 Cards in this Set
- Front
- Back
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Metformin HCl
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Glucophage
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Indication, MOA for Metformin/Glucophage
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For T2DM w/ diet and exercise or in combo with sulfonylurea
MOA: decrease hepatic gluconeogenesis and intestinal glucose absorption, increases peripheral insulin sensitivity (no release of insulin) |
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Half-life and contraindications of metformin/glucophage
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Half life: 1.3-4.5 hours, no protein binding, rapid renal excretion (positive charged)
Decrease in B12 and folate absorption, contraindicated in hepatic and renal failure, hx of lactic acidosis, STOP if MI or septicemia |
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MOA of Sulfonylureas
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Stimulates insulin release from beta cells by binding and blocking ATP-ase sensitive K+ channel, floods cell with Ca2+, depolarization releases insulin
May decrease hepatic clearance of insulin |
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What is the difference of all these agents? (different generations)
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Biological half-life
Second generation are 100X more potent All are hepatic ally metabolized |
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AE of Sulfonylureas
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Hypoglycemia (may appear as stroke in elderly)
Many drug interactions due to inhibition/induction Difulfiram-like reactions with alcohol (esp. with chlorpropamide) |
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Contraindication of Sulfonylureas
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Type 1 patients, pregnancy, lactation, hepatic or renal failure
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What are 4 first generation sulfonylureas and their serum half-life and metabolite types?
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Tolazamide, t1/2= 7 hours, active metabolites
Tolbutamide, t1/2 = 4.5-6.5 hours, no active metabolites Chlorpropamide/Diabinese (brand), t1/2 =36 hours (avoid in elderly), active metabolites --> long half life due to CYP mediated hydroxylation Acetohexamide, t1/2 = 6-8 hours, active metabolites |
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What are 2 second generation sulfonylureas and their serum half-life and metabolite types?
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Glipizide/Glucotrol (brand), t1/2 = 2-4 hours, no active metabolites
Glyburide (Glibenclamide) - Diabeta (brand) t1/2 if micronized = 4 hours, weak active metabolites (use in elderly) t1/2 if nonmicronized = 10 hours, weak active metabolites |
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What is a third generation sulfonylurea?
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Glimepride/Amaryl (brand), t1/2 = 9 hours, active metabolites
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What is the MOA of 3rd generation sulfonylureas?
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Same as 1st and 2nd generation plus:
Translocation of GLUT4 to cell surface (insulin like activity) and binds to different protein than usual sulfonylurea receptor on beta cell |
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What is important for thizaolidinediones?
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Drugs only work in presence of insulin!
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What is the MOA of thiazolidinediones?
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Increase activity of nuclear receptor PPAR-gamma that regulates genes responsible for control of glucose and insulin metabolism in adipose, liver and skeletal muscle tissues --> increases tissue sensitivity
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What do you have to watch for in thiazolidinediones?
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Hepatic failure: monitor tranaminase levels,
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What are 2 types of thiazolidinediones?
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Rosiglitzazone maleate/Avandia (brand)
Pioglitazone HCl/Actos (brand) |
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What enzymes are Avandia and Actos metabolized by?
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Avandia: CYP2C8 and 2C9 (lesser)
Actos: CYP3A4 |
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What does Actos do to oral contraceptives?
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Decreases its efficacy, stimulates ovulation
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What is thiazolidinediones contraindicated for?
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Patients at risk for heart failure: can exacerbate heart failure and pulmonary edema especially in patients with LVF or chronic renal insufficiency
Edema: common side effect but weight gain should not be more than 6.6 lbs (3kg) |
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What is a new activity for thiazolidinediones?
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Inhibition of monamine oxidase B (degrades NT): prevent degradation of dopamine could be used in parkinsons
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What is a non-sulfonylurea analog of glyburide drug?
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Repaglinide/Prandin (brand)
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What is Prandin used for?
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T2DM w/ diet and exercise or combo with thiazolidinedione
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What is the MOA of prandin?
What enzyme is prandin metabolized by? |
Same as sulfonylureas
Metabolized by CYP3A4 |
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What is a D-phenylglycine analog diabetic drug?
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Nateglinide/Starlix (brand) for T2DM
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What is the MOA of Starlix?
What enzymes metabolize it? |
Same as sulfonylureas
Highly selective with low affinity for heart and skeletal muscle K+ channels, 90% albumin binding, metabolized by CYP2C9 (primary) and CYP3A4 |
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What are examples of alpha-glucosidase inhibitors?
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Acarbose/Precose (brand)
Miglitol/Glyset (brand) |
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What is the indication and MOA of alpha-glucosidase inhibitors?
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Decreases carbohydrate absorption by inhibiting alpha-glucosidase (amino group in structure prevents protonation of glycosidic bond in saccharides by a COOH group in the active site)
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What are the main AE for alpha-glucosidase inhibitors?
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Diarrhea, flatulence, GI problems: diminish /p 2 week use
Acarbose: minimal absorption, but at high doses: increase in serum transaminates (hepatic toxicity) Miglitol: rapid and complete systemic absorption |
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What forms in the gut associated with alpha-glucosidase inhibitors?
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Pneumatosis Cystoides Intestinalis
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Examples of combo products for diabetic medications
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Rosiglitazone maleate + metformin HCl = Avandamet
Glyburide + metformin HCl = Glucovance Rosiglitazon Maleate + Glimepiride = Avandaryl Pioglitazone + Metformin HCl = ACTOplus Met Repaglinide + Metformin = PrandiMet |
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What are examples of recombinant/chemically modified insulins?
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Insulin glulisine/Apidra: rapid acting
Insulin detemir/Levemir: long acting Insulin glargine/Lantus Insulin aspart/Novolog: rapid acting (3-5 hour) Insulin lispro/Humalog: rapid acting (3-5 hour) |
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How is Apidra produced?
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Rapid acting product recombinant site directed mutation human insulin produced in E. coli
Lysine replaces Asparagine at position 3 and glutamic acid replaces lysine at position 29 |
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How is Levemir produced?
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Long acting product recombinant site directed mutation human insulin produced by Saccharomyces cerevisiae followed by chemical modification with a fatty acid (98% bound to albumin)
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MOA of Lantus (basic)
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Microprecipitates in SQ tissue prolonging duration, cancer risk
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What are examples of recombinant/chemically modified/synthetic polypeptides?
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Exenatide/Byetta: incretin mimetic releases insulin
Pramlintide acetate/Symlin: synthetic analog of human amylin: made in beta cells contributes to glucose postprandial |
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What are insulin mimetics?
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Small non-peptide molecules that bind the insulin receptor
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What is Duetact?
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Combo product of Pioglitazone HCl + Glimepiride
Pioglitazone targets insulin resistance and Glimepiride increases insulin produced in pancreas |
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What are incretins?
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Peptide hormones released from the gut in response to ingestion of carbohydrate (blunted effect in T2DM)
GLP-1 stimulates insulin release GIP (glucose dependent insulinotropic peptide) enhances exocytosis of insulin containing granules |
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I.V. glucose does not cause release of what?
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Incretins (only oral glucose releases incretins)
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How are incretins metabolized?
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DPP-IV (dipeptidyl peptidase-IV) cause brief action of incretins
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What is an anti diabetic drug that is not a substrate for DPP-IV?
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Exenatide/Byetta: incretin mimetic/GLP-1 agonist (from lizard spit! but link to acute pancreatitis and acute renal failure)
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What is an anti diabetic drug that is a peptide analog and incretin mimetic?
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Iiraglutide/Victoza: injection for SQ anytime of day, rDNA origin
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What is the MOA and black box warning for Victoza?
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MOA: Incretin mimetic, GLP-1 agonist
Risk of Thyroid C-Cell Tumors |
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What is an anti diabetic drug that inhibits DPP-IV?
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Sitagliptin phosphate/Januvia
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What is the indication and MOA of Januvia?
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Indication: T2DM (not for type 1), combo with metformin or thiazolidinediones
MOA: inhibit DPP-IV, increase levels of incretins --> increase insulin release and decrease glucagon release |
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When do you need to modify dosing of Januvia?
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In moderate/end-stage renal failure as function of CrCl = 79% excreted via OCT active tubular secretion as UNCHANGED drug
Doesn't inhibit or induce CYP3A4, no extensive proton binding, substrate for P-GP |
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What is a potential AE of Januvia?
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Inhibit DPP-IV --> increase in peptides normally cleaved by DPP-IV (neuropeptides, cytokines, chemokines)
Cytokines and Chemokines important in immune repsonse: inhibit degredation: decreased response |
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What is another DPP-IV inhibitor?
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Saxagliptin/Onglyza
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What is the MOA, metabolism and AE of Onglyza?
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MOA: DPP-IV inhibitor
Metabolism: CYP3A4/5 to active metabolite AE: decreased lymphocyte count (increase UTI,URI), hypoglycemia, uticaria, acute pancreatitis, HA |
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What is a new DPP-IV inhibitor that came out in 2011?
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Combo of Metformin + DPP-IV inhibitor/Jentadueto
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What is the limitation of use, metabolism, DI and AE of Jentadueto?
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NOT USED IN T1DM or treatment of diabetic ketoacidosis
Metabolism: 90% excreted unchanged with 80% hepatobiliary DI: substrate for P-gP, CYP3A4 inducer and mild inhibitor AE: when used with insulin secretagogues (sulfonylurea): higher risk for hypoglycemia |
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What is a new DPP-IV inhibitor that came out in 2013?
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Alogliptin Tablets/Nesina
Alogliptin + Metformin: Kazano Alogliptin + Pioglitazone: Oseni |
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What are side effects of Nesina, Kazano, Oseni?
What is it not metabolized by? |
Acute pancreatitis, hypoglycemia, anaphylaxis, angioedema, steve-johnson syndrome, fatal hepatic failure
Not metabolized by CYP enzymes, excreted unchanged in urine and feces, EXPENSIVE |
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What is a new SGLT2 Inhibitor drug?
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Canagliflozin/Invokana
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What is the MOA, Limitations and DI and AE in Invokana?
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MOA: sodium-glucose co-transporter 2 inhibit: blocks glucose reabsorption in kidney
Limitation: NOT for T1DM or ketoacidosis (diabetic) DI: UGT inducers (O-glucronidation is major metabolic elimination UGT1A9 and UGT2B4 to two inactive metabolites) and CYP3A4 mediated metabolism AE: Vaginal yeast infections and UTI (diuretic affect = hypotension, hyperkalemia), |
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When do you discontinue Invokana use?
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When eGFR falls below 45 mL/min/1.73m2
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What is an old drug but new indication marked previously as parlodel for hyperprolactinemia and parkinsons?
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Bromocriptine mesylate/Cycloset (brand)
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What is the MOA and AE of Cycloset?
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Dopamine receptor agonist: increases dopamine levels early in day to reset circadian rhythm and improves metabolism problems
N/V, fatigue, HA, dizziness, |
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What is a human derived platelet growth factor recombinant biotechnology product used in diabetic ulcers?
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Becaplermin/Regranex
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What is the indication, contraindications and warning in Regranex use?
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Indication: 0.1% topical gel for treatment of lower extremity diabetic neuropathic ulcers (only use if blood supply if adequate)
Contra: if known neoplasm at site of admin Warning: Use caution in patient with any known or previous malignancy |
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What is a bile acid sequestrate for diabetes?
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Colesevelam HCl = Welchol
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What is the MOA of Welchol?
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Bile acid sequestrate to improve glycemic control
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